Interaction of chitosan derivatives with cell membrane models in a biologically relevant medium.

HYPOTHESIS: The interaction of chitosan, a natural biopolymer with various biomedical applications, with lipid Langmuir films has been widely investigated as a simple model for cell membranes. However, to ensure polymer solubility, up to now only acidic subphases with pH significantly below biological fluids have been used. To increase the biological significance of these investigations, here we evaluated the effects of two chitosan derivatives (low molecular weight - CH, and positively charged - CH-P40) on phospholipid films (either zwitterionic DPPC or anionic DPPG) using phosphate buffered saline solutions (PBS) as a subphase. EXPERIMENTS: Surface pressure - area (π-A) isotherms were used to evaluate the expansion and changes in film elasticity, while Sum-Frequency Generation (SFG) vibrational spectroscopy provided information about the chain conformation of lipids. FINDINGS: It was found that chitosans caused a small expansion of the DPPC film by its insertion within the monolayer. In contrast, they distinctly expanded DPPG monolayers by both chitosan insertion within the lipid monolayer and by interacting with the anionic head group. Therefore, PBS buffer can be used as a subphase for more biologically relevant studies of chitosan interactions with Langmuir films, shedding light on why chitosan is antibacterial but not toxic to mammals, as the interaction mechanism depends on lipid headgroup charge.

The interaction of mefloquine hydrochloride with cell membrane models at the air-water interface is modulated by the monolayer lipid composition.

The antiparasitic properties of antiparasitic drugs are believed to be associated with their interactions with the protozoan membrane, encouraging research on the identification of membrane sites capable of drug binding. In this study, we investigated the interaction of mefloquine hydrochloride, known to be effective against malaria, with cell membrane models represented by Langmuir monolayers of selected lipids. It is shown that even small amounts of the drug affect the surface pressure-area isotherms as well as surface vibrational spectra of some lipid monolayers, which points to a significant interaction. The effects on the latter depend on the electrical charge of the monolayer-forming molecules, with the drug activity being particularly distinctive for negatively charged lipids. Therefore, the lipid composition of the monolayer modulates the interaction with the lipophilic drug, which may have important implications in understanding how the drug acts on specific sites of the protozoan membrane.